Radiotherapy + Androgen Deprivation Therapy for Prostate Cancer

Overseen By Benjamin Spieler, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Antiandrogens, LHRH agonists

Disqualifiers: Prior pelvic radiotherapy, Androgen ablation, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 14 months

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of a new type of radiation therapy, called LEAD RT, for treating certain stages of prostate cancer. It will evaluate this therapy both with and without additional hormone therapy, known as androgen deprivation therapy (ADT), which sometimes lowers male hormone levels that can fuel prostate cancer growth. The trial is open to men with prostate cancer that has not spread and who have not undergone previous pelvic radiation or prostate removal surgery. Researchers will monitor participants over several years to assess the treatment's long-term effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anti-androgen therapy or androgen deprivation therapy, there are specific timing requirements for starting these treatments during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments tested in this trial have been safe in earlier studies.

For the FTLEAD treatment, which involves high-dose radiation therapy, previous studies found it feasible and generally well-tolerated. Some patients experienced side effects, but these were usually mild and manageable.

HypoLEAD, another type of radiation therapy, has demonstrated effectiveness in studies and has a safety profile similar to traditional radiation treatments. Some patients experienced urinary or bowel symptoms, but these were typically not severe.

The ultra-short-term androgen deprivation therapy (ADT) using relugolix has been studied in various settings, including this trial. Research shows that relugolix effectively lowers testosterone levels and is well-tolerated. It also carries a lower risk of serious heart-related side effects compared to other ADT options.

Overall, these treatments have been tested in earlier studies and are generally safe for most patients. While side effects can occur, they are often mild and manageable with proper care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they bring innovative approaches to radiation therapy and hormone treatment. Unlike the usual lengthy androgen deprivation therapies, the ultra short-term ADT used in some trial arms aims to reduce side effects while maintaining effectiveness. The Focal Therapy lattice extreme ablative dose (FTLEAD) offers a targeted approach, potentially minimizing damage to surrounding healthy tissues. Additionally, HypoLEAD involves a hypofractionated radiation schedule, which can shorten treatment time and increase convenience for patients compared to traditional radiotherapy regimens. These treatments represent a significant shift towards more personalized and less invasive cancer care.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research shows that both FTLEAD and HypoLEAD radiotherapy are promising treatments for prostate cancer. In this trial, participants in different arms will receive either FTLEAD or HypoLEAD. Studies have found that FTLEAD can precisely target the tumor with high doses of radiation, resulting in a five-year survival rate of 97% for some patients. HypoLEAD has also effectively delivered targeted, high-dose radiation, with previous studies meeting the necessary standards for radiation distribution.

Additionally, some participants will receive a short-term hormone therapy called relugolix, which has been shown to quickly lower testosterone levels, helping to slow the growth of prostate cancer. Clinical trials demonstrated that relugolix successfully reduced and maintained low testosterone levels in over 98% of patients. This combination of treatments in the various arms of this trial aims to effectively target and manage prostate cancer with promising results. ^{1 2 3 6 7}

Who Is on the Research Team?

Benjamin Spieler, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Men aged 35-85 with confirmed adenocarcinoma of the prostate, stages T1-T3, Gleason score 6-10, and PSA ≤100 ng/mL. They must have no evidence of metastasis or prior pelvic radiotherapy/prostate surgery and be able to consent. Those with concurrent active cancers (except certain skin cancers/early-stage leukemia) or a history of cancer in remission for less than 5 years are excluded.

Inclusion Criteria

The projected duration must not exceed 30 months.

I can't have iodine or gadolinium contrast because of an allergy or kidney issues but can still join.

My MRI shows a suspicious area in my prostate.

Exclusion Criteria

I have had or am planning to have major prostate surgery.

My scans show cancer spread to small lymph nodes or distant areas, making me ineligible for FTLEAD but possibly for HypoLEAD.

I don't have any active cancer except for non-spreading skin cancer or early-stage CLL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lattice Extreme Ablative Dose (LEAD) RT with or without ultra short-term androgen deprivation therapy (ADT), followed by hypofractionated RT

Up to 14 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of biochemical disease failure and treatment-related toxicity

5.5-8 years

What Are the Treatments Tested in This Trial?

Interventions

• ADT Standard of Care
• FTLEAD
• HypoLEAD
• Ultra-Short-Term Androgen Deprivation Therapy with Relugolix

Trial Overview The UAdapt Trial is testing single high-dose radiotherapy (SDRT) on patients with favorable and unfavorable risk prostate cancer. It includes standard ADT care, FTLEAD, HypoLEAD treatments, and ultra-short-term Androgen Deprivation Therapy using Relugolix to see if they prevent disease failure one year post-radiotherapy.

How Is the Trial Designed?

Group I: Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), uSTADT, Arm D Experimental Treatment 4 Interventions

Participants in this group will receive LEAD RT with ultra short-term ADT followed by moderately hypofractionated RT (HypoLEAD) and standard of care ADT and will be followed for 5.5-8 years.

Group II: Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), Arm C Experimental Treatment 3 Interventions

Participants in this group will receive LEAD RT followed by moderately hypofractionated RT (HypoLEAD) and standard of care androgen deprivation therapy and will be followed for 5.5-8 years.

Group III: Focal Therapy lattice extreme ablative dose (FTLEAD), uSTADT, Arm B Experimental Treatment 2 Interventions

Participants in this group will receive the FTLEAD treatment and ultra short-term androgen deprivation therapy (ADT) and will be followed for up to 5.5 years.

Group IV: Focal Therapy lattice extreme ablative dose (FTLEAD), RT Only, Arm A Experimental Treatment 1 Intervention

Participants in this group will receive the FTLEAD treatment only and will be followed for up to 5.5 years.

FTLEAD is already approved in United States for the following indications:

Approved in United States as Lattice Extreme Ablative Dose (LEAD) RT for:

• Non-metastatic prostate cancer

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

In intermediate-risk prostate cancer patients (520 participants), androgen deprivation therapy (ADT) significantly improved biochemical relapse-free rates, particularly in those with multiple risk factors, indicating that short-term ADT (≤6 months) is beneficial.

For high-risk prostate cancer patients (555 participants), longer ADT durations (>6 months) were associated with better biochemical relapse-free rates, especially for those with multiple high-risk factors, suggesting that ADT for ≥21 months may be optimal when combined with high-dose proton beam therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. Murakami, M., Ishikawa, H., Shimizu, S., et al.[2020]

In a study of 289 high-risk prostate cancer patients treated with external beam radiotherapy and androgen deprivation therapy (ADT), increasing the radiotherapy dose significantly improved PSA relapse-free survival (PRFS), with rates of 72.7% for 66 Gy, 81.6% for 72 Gy, and 90.3% for 78 Gy after 4 years.

The benefits of dose escalation were particularly notable in patients with multiple high-risk factors (H-1 subgroup), while those with a single high-risk factor (H-2 subgroup) did not show improved PRFS with higher doses, indicating that treatment strategies may need to be tailored based on individual risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation of external beam radiotherapy for high-risk prostate cancer-Impact of multiple high-risk factor. Umezawa, R., Inaba, K., Nakamura, S., et al.[2022]

In a study of 263 patients with locally advanced prostate cancer, combining androgen-deprivation therapy (ADT) with external beam radiation therapy (EBRT) significantly improved progression-free survival (PFS) rates at 8 years (48% vs 7%) compared to ADT alone, indicating a strong oncological benefit of the combination treatment.

The risk of death from prostate cancer was reduced by nearly half in the ADT+EBRT group, demonstrating that this combination not only prolongs survival without disease progression but also enhances disease-specific survival, despite similar overall survival rates between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. Sargos, P., Mottet, N., Bellera, C., et al.[2020]

In a study of 4,537 patients with T1-T2 prostate cancer treated with external beam radiotherapy, higher radiation doses (70-76 Gy) shifted the criteria for low-risk groups, indicating that patients with higher initial PSA levels and Gleason scores were classified as low-risk at these doses.

The findings suggest that traditional risk group classifications, based on lower radiation doses, may not accurately reflect the risk of clinical failure for patients receiving higher doses, highlighting the need for ongoing reevaluation of risk classifications in light of evolving treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing external beam dose for T1-T2 prostate cancer: effect on risk groups. Thames, HD., Kuban, DA., DeSilvio, ML., et al.[2007]

Higher doses of external beam radiation therapy (EBRT) greater than 75 Gy significantly improve prognosis in high-risk prostate cancer patients, as shown in multiple randomized controlled trials including RTOG 94-06.

Carbon ion therapy has demonstrated promising biochemical recurrence-free survival rates in high-risk prostate cancer patients, indicating that particle therapy is a valid treatment option alongside traditional radiation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of high-risk prostate cancer: radiation therapy and hormonal therapy. Nomiya, T., Tsuji, H., Toyama, S., et al.[2013]

In a study of 105 patients with high-risk prostate cancer, the combination of androgen deprivation therapy (ADT) and moderate hypofractionated radiation therapy (HypoRT) was found to be well tolerated, with low rates of acute and late toxicity; only 17% experienced grade 2 or higher gastrointestinal or genitourinary toxicity, and no severe grade 4 or 5 toxicities were reported.

The treatment regimen resulted in an 82% progression-free survival rate at 48 months, demonstrating its efficacy while also shortening the overall treatment duration, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiation therapy. Faria, S., Ruo, R., Cury, F., et al.[2018]

In a study of 1,290 high-risk prostate cancer patients treated with external beam radiation therapy, androgen deprivation therapy (ADT) significantly reduced the risk of biochemical failure and distant metastasis compared to no ADT, highlighting its efficacy in improving patient outcomes.

Patients receiving more than 24 months of ADT experienced a greater benefit in terms of PSA failure rates and distant metastasis-free survival, particularly in those who received low-dose radiation, suggesting that longer ADT duration may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the Optimum Use of Androgen-Deprivation Therapy in High-Risk Prostate Cancer Patients Undergoing External Beam Radiation Therapy. Ludwig, MS., Kuban, DA., Strom, SS., et al.[2022]

In a study involving 397 patients with high-risk prostate cancer, the addition of adjuvant chemotherapy to long-term androgen suppression and radiation therapy did not significantly improve overall survival or other key outcomes compared to radiation therapy alone.

The trial was halted early due to increased thromboembolic toxicity in the chemotherapy group, highlighting safety concerns associated with this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902. Rosenthal, SA., Hunt, D., Sartor, AO., et al.[2022]

In a study of 2028 men with localized prostate cancer, adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved disease-specific mortality (DSM) significantly, with a 10-year DSM of 3% for combined therapy compared to 7% for RT alone.

While overall survival (OS) rates converged around 15 years, the addition of 4 months of ADT provided an estimated additional 6 months of life, with low rates of severe side effects, indicating that the combined treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial. Jones, CU., Pugh, SL., Sandler, HM., et al.[2023]

In a study involving 3215 men with prostate cancer, the addition of androgen-deprivation therapy (ADT) to standard-dose radiotherapy (SDRT) showed significantly greater benefits than simply increasing the radiotherapy dose from 70 Gy to 80 Gy.

The developed nomograms provided personalized estimates of treatment outcomes, indicating that for intermediate-risk and high-risk patients, longer durations of ADT (≥3 months) are more effective than modest escalations in radiotherapy dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of dose-escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms. Stoyanova, R., Pahlajani, NH., Egleston, BL., et al.[2021]

Androgen deprivation therapy combined with radiation therapy is a standard treatment for intermediate to high-risk localized and locally advanced prostate cancer, showing effective management of the disease.

Emerging hormonal therapies are being explored for their potential benefits in earlier stages of prostate cancer, particularly in combination with radiation, highlighting a promising area of research for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation of Androgen Deprivation Therapy Combined With Radiotherapy for N0 M0 Prostate Cancer. Barata, P., Layton, J., Lewis, B., et al.[2021]

In a Phase I study involving 66 high-risk prostate cancer patients, hypofractionated accelerated radiotherapy combined with an intensity-modulated boost showed acceptable levels of acute toxicity, with most side effects being mild (Grade 1-2) and resolving within 3 months after treatment.

Only 5 patients experienced acute Grade 3 genitourinary toxicities, while no patients suffered from severe gastrointestinal or higher-grade genitourinary toxicities, indicating that this treatment approach is both feasible and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results. Lim, TS., Cheung, PC., Loblaw, DA., et al.[2018]

Advancements in radiotherapy techniques, such as 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT), have allowed for higher radiation doses (up to 80 Gy and beyond) to be safely delivered to localized prostate cancer, improving treatment outcomes while reducing side effects like rectal toxicity.

The combination of radiotherapy with androgen deprivation therapy enhances treatment efficacy by reducing tumor size and improving overall survival, particularly in more advanced prostate cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technological advances in radiotherapy for the treatment of localised prostate cancer. Mangar, SA., Huddart, RA., Parker, CC., et al.[2006]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32084522/

Phase I Trial of MRI-Guided Prostate Cancer Lattice Extreme ... Results: Dosimetric parameters were satisfactorily met. Median follow-up was 66 months.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301620302182

Phase I Trial of MRI-Guided Prostate Cancer Lattice ... For some high-risk patients, the distal seminal vesicles and pelvic lymph nodes received 56 Gy at 1.47 Gy/fraction concurrently in 38 fractions. The total dose ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06111313

NCT06111313 | The University of Miami Adapt (UAdapt) Trial In focal therapy lattice extreme ablative (FTLEAD) RT, the multiparametric-MRI (mpMRI) defined gross tumor volume (GTV) will receive 16-20 Gy in a single ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468211/

Focal Therapy for Localized Prostate Cancer: A Case ... In 2024, the five-year cancer-specific survival (CSS) was estimated to be 97% in the USA alone [1]. Traditional treatments for PCa have been ...

5. mdpi.com mdpi.com/2072-6694/15/19/4888

Focal Boost in Prostate Cancer Radiotherapy: A Review of ... For instance, the RT01 trial [118] demonstrated an 11% improvement in biochemical relapse-free survival (bRFS) with a 15% increase in prescribed dose. Based on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10572027/

Focal Boost in Prostate Cancer Radiotherapy: A Review of ... Urethral doses above 80 Gy have been linked to an increased risk of urethral strictures [127]. However, focal boost studies, such as the Focal Lesion Ablative ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01411319?term=LEAD&viewType=Table&rank=3&tab=results

MRI-Guided Lattice Extreme Ablative Dose Radiotherapy ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...